{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:31:57Z","timestamp":1775716317808,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,3,15]],"date-time":"2007-03-15T00:00:00Z","timestamp":1173916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Aggregation and deposition of amyloid beta (A\u03b2) in the brain is thought to be central to the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that cerebrospinal fluid (CSF) A\u03b2 levels are strongly correlated with AD status and progression, and may be a meaningful endophenotype for AD. Mutations in presenilin 1 (<jats:italic>PSEN1<\/jats:italic>) are known to cause AD and change A\u03b2 levels. In this study, we have investigated DNA sequence variation in the presenilin (<jats:italic>PSEN1<\/jats:italic>) gene using CSF A\u03b2 levels as an endophenotype for AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We sequenced the exons and flanking intronic regions of <jats:italic>PSEN1<\/jats:italic> in clinically characterized research subjects with extreme values of CSF A\u03b2 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This novel approach led directly to the identification of a disease\u2010causing mutation in a family with late\u2010onset AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This finding suggests that CSF A\u03b2 may be a useful endophenotype for genetic studies of AD. Our results also suggest that <jats:italic>PSEN1<\/jats:italic> mutations can cause AD with a large range in age of onset, spanning both early\u2010 and late\u2010onset AD. Ann Neurol 2007;61:446\u2013453<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21099","type":"journal-article","created":{"date-parts":[[2007,3,15]],"date-time":"2007-03-15T23:40:34Z","timestamp":1174002034000},"page":"446-453","source":"Crossref","is-referenced-by-count":68,"title":["Extreme cerebrospinal fluid amyloid \u03b2 levels identify family with late\u2010onset Alzheimer's disease presenilin 1 mutation"],"prefix":"10.1002","volume":"61","author":[{"given":"John S. 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